The study asks how to combine sub-micrometer hydrogel patterning with larger tissue-engineering constructs. A Type II Eosin Y/triethanolamine photoinitiating system reduces heat generation in projection two-photon lithography. Experiments demonstrate high-fidelity hydrogel microparticles, sub-micrometer line features, and 815 particles per hour for the reported 250-micrometer-high geometry. Extrusion assembles these microparticles into scaffolds; cell-culture experiments show pore-dependent infiltration and groove-dependent alignment, supported by simplified particle and coarse-grained cell si

A hydrogel particle can offer cells a way in—and a direction to grow. This paper makes those microscopic instructions faster to manufacture, then assembles them into larger scaffolds.

Precision gives each particle a job. Projection gives production a new pace.

Give cells a landscape.

Open the axial channel. Carve the outer surface. Discover how two distinct features give cells different instructions.

A small opening keeps cells outside.

Conceptual animation · cell observations after 7 days Movement compressed for exploration.

Inside—or along?

The central lumen provides access. Longitudinal surface grooves provide direction. Change each one and compare the response.

Cells remained outside the lumen after 7 days. An opening smaller than the average nucleus restricts access.

Without longitudinal grooves, cells had a broad range of orientations.

Suppress the heat.

Excited-state quenching in the Type II system reduces heating while producing radicals for polymerization. Parallel exposure can then retain fine detail.

Encode the environment.

Open lumens let cells enter. Narrow longitudinal grooves favor alignment. These are separate structural cues, built into the same particle.

Carry the cues upward.

Extrusion aligns the particles into larger scaffolds. The study demonstrates organized cell growth, vessel-like linings, and fibroblast matrix formation in vitro.

Geometry becomes a biological cue.

The animation makes the mechanism easy to explore. The paper's microscopy shows how living cells actually respond to the fabricated hydrogel particles.

The fabrication-to-biology sequence matters.

Guan et al., Supplementary Movie S1, CC BY 4.0; resized and transcoded.

Guan et al., Supplementary Movie S3, CC BY 4.0; first 20-second excerpt, resized and transcoded.

In projection two-photon lithography, spatial and temporal focusing confine polymerization to a thin focal region. A digital micromirror device patterns a full two-dimensional cross-section, and motion of the fabrication stage builds the three-dimensional structure.

The Type II formulation combines Eosin Y, triethanolamine (TEOA), N-vinyl-2-pyrrolidone, and methacrylated gelatin (GelMA). TEOA quenches excited singlet and triplet states of Eosin Y, promoting radical generation while suppressing nonradiative heat. The paper's GelMA ink contains 20% w/v GelMA, 0.4 mM Eosin Y, 1% v/v TEOA, and 5% v/v NVP. The method also prints modified silk fibroin, hyaluronic acid, and dextran hydrogels.

The reported fabrication uses 350 mW laser power. Sub-micrometer line features are demonstrated at this setting; the throughput of 815 particles/hour applies to the reported 250 μm-high geometry. See Sections 2.1–2.2 and Methods 4.5.

The studio preserves qualitative trends rather than predicting cell fractions, migration speeds, or growth. The lumen control follows the paper's 7-day NIH 3T3 fibroblast experiments on 90 μm outer-diameter particles. The surface control follows 7-day rat cortical-cell experiments and fibroblast confirmation: 2–4 μm grooves favor alignment; wider grooves and smooth surfaces diminish it.

Cell movement and transitions are compressed into seconds for exploration. Surface cells and cells entering the axial lumen are drawn separately. The 3D rod, cells, light, and extrusion are conceptual drawings rather than microscopy or a computed reconstruction.

The paper's coarse-grained cell simulations relate contact guidance to focal adhesions and membrane bending. Its simplified particle-flow simulations omit viscoelasticity and weak interparticle interactions. The assembly control illustrates reported tendencies: greater aspect ratio and particle concentration improve alignment. It does not calculate a numerical extrusion optimum.

The strategy links small-scale control with larger-scale assembly: manufacture each particle's cues, then arrange those particles into a scaffold. In the reported experiments, grooved-particle scaffolds supported greater collagen formation and tensile properties after 3 weeks of fibroblast culture than spherical-particle controls. Endothelial cells formed a vessel-like lining within lumens after 5 days.

A separate comparison of particles with 64 μm lumens versus solid particles measured scaffold porosity of 56% versus 35%, and F-actin coverage of 57% versus 25%. These values describe that comparison, not the four lumen settings in the studio. The biological demonstrations were performed in vitro. See Sections 2.3–2.5.

Guan et al., Heat-Suppressing Projection Two-Photon Lithography Enables High-Throughput Sub-Micrometer Manufacturing of Biopolymer Hydrogels for Tissue Engineering, Advanced Science, 2026. DOI: 10.1002/advs.76938.

The displayed source figures are cropped reproductions under the article’s Creative Commons Attribution 4.0 license. Captions have been adapted for this companion. The graphical abstract is an AI-generated conceptual illustration based on this paper.

The paper's supporting material contains additional fabrication, cell-culture, and simulation results, plus Movies S1–S3. Supporting document ↗ · Supplementary movies ↗

A closer reading. A different way in.

Explore the structures, then follow the evidence.

Heat-Suppressing Projection Two-Photon Lithography Enables High-Throughput Sub-Micrometer Manufacturing of Biopolymer Hydrogels for Tissue Engineering

Qifeng Guan, Yanzhe Fu, Xiangyu Xu, Naitao Li, Sen Hou, Kai Wang, Yufan Wang, Jiakun Li, Ping Li, Jiebo Li, Lizhen Wang, and Yubo Fan.

Advanced Science · 2026 · DOI: 10.1002/advs.76938

Source figures: CC BY 4.0, with cropping, resizing, and adapted captions as noted. Conceptual illustration and interactive teaching animations accompany the source evidence.